The Laboratory of Genetics and Physiology explores genetic programs that control the establishment and functional differentiation of diverse cell types, including mammary epithelium, hematopoietic lineages, liver, pancreas and skin. A common denominator to these cell types is their need for cytokines to control cell proliferation, survival and differentiation and death. In particular, this laboratory investigates the Jak/Stat pathway, which is activated by a diverse set of cytokines, including interleukins, growth hormone and prolactin. Moreover, authentic biological functions of these cytokine pathways are discovered and studied through the use of experimental mouse genetics, with an emphasis on the development of the mammary gland, and more recently the hematopoietic system and pancreatic beta cells. Over the past year LGP extended its focus on genetic pathways that control key aspects of cell specification in mammary tissue. Thereby, we hope to obtain a comprehensive understanding of a developmental process emanating from the mammary stem cells and finally yielding a differentiated cell secreting milk. [unreadable] [unreadable] During this reporting period, LGP discovered and published that the Notch signaling pathway is instrumental in the establishment of defined cell lineages in mammary tissue. Through the inactivation of all Notch receptors in mammary stem cells we discovered that the development of the alveolar luminal lineage (the milk secreting cells) is dependent on the presence of Notch signaling. In addition LGP published work defining the role of the transcription factors Stat5a and Stat5b in the hematopoitic system. LGP continued to engage in collaborations on genetic pathways in mammary development and the immune system with extramural researchers, which resulted in publications.